Because tumor growth requires new blood vessel formation, agents that inhibit tumor-induced angiogenesis in preclinical models should be well tolerated by patients and could produce clinically relevant antitumor responses. We hypothesize: that interpatient pharmacokinetic (PK) and pharmacodynamic (PD) variability can be accounted for, at least in part, by determining a drug metabolism profile for each patient; that the results of agent-specific biological assays on tumor or plasma from patients will be predictive for clinical antitumor effect; and that metabolic and biologic data obtained in Phase I trails will be useful in the design of Phase II efficacy trials. We have extensive prior experience in the pharmacologic evaluation of new agents; determination of patient's metabolic profiles; biological characterization of agents that inhibit tumor angiogenesis; and the determination of growth factor expression in human tumors. We propose to combine these capabilities to conduct early clinical trials of agents that inhibit tumor-induced angiogenesis. During he first year an agent that inhibits endothelial cell growth, TNP-470, will be studied alone and then in combination with pentosan polysulfate (PPS), and agent that inhibits the activity of Heparin Binding Growth Factors (HBGFs). Because of promising antitumor and anti-angiogenic activity of TNP-470 in preclinical models of human CNS tumors, recommended Phase II doses (RP2Ds) for patients with CNS tumors will also be determined. An additional 10 patients with accessible tumor and measurable disease will be studied at the RP2D to obtain additional data on PK/PD, metabolic profiles and correlative biological assays on tumor and plasma. Accrual of additional female and minority patients at the RP2D will be permitted to explore differences in metabolic profiles and PK parameters in these populations. Detailed methodology is provided regarding the proposed clinical protocols; drug assays; metabolic characterization of patients; measures of tumor-induced endothelial cell growth and plasma anti-HBGF activity; and HBGF expression in human tumors specimens. Agents to be studied in subsequent years will be determined from our preclinical data in consultation with the NCI and could include recombinant human (rHu) Interferon-alfa, rHu platelet factor IV and third generation anti-HBGF polyanions.